Certain 2,4-disubstituted thiadiazolidinone (TDZD) compounds have been reported to be useful as enzyme inhibitors of glycogen synthase kinase 3β, or GSK-3. See, e.g., US 2003/0195238A1, US 2005/0222220A1. Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase comprised of α- and β-isoforms that are each encoded by distinct genes (Coghlan et al., Chemistry & Biology, 7, 793-803 (2000); Kim and Kimmel, Curr. Opinion Genetics Dev., 10, 508-514 (2000)). The threonine/serine kinase glycogen synthase kinase-3 (GSK-3) fulfills a pivotal role in various receptor-linked signalling pathways (Doble, B W, Woodgett, J R J. Cell Sci. 2003, 116:1175-1186). Dysregulation within these pathways is considered a crucial event in the development of several prevalent human disorders, such as type II diabetes (Kaidanovich O, Eldar-Finkelman H, Expert Opin. Ther. Targets, 2002, 6:555-561), Alzheimer's disease (Grimes C A, Jope R S, Prog. Neurobiol. 2001, 65:391-426), CNS disorders such as manic depressive disorder and neurodegenerative diseases, and chronic inflammatory disorders (Hoeflich K P, Luo J, Rubie E A, Tsao M S, Jin O, Woodgett J, Nature 2000, 406:86-90).
Additionally certain TDZD compounds are reported to be non-competitive GSK-3β inhibitors, which demonstrate promise as AD pharmacotherapy agents. Martinez, A. et al. J. Med. Chem., 45, 1292-1299 (2002).
It is now discovered that TDZD compounds are useful in treating disorders different and distinguishable from those previously reported.